Renpenning syndrome or non-specific X-linked mental retardation is a common term used to describe a rather heterogenous subgroup of male mental retardates which may account for 20% of the retarded male population. In some families with this disorder, the affected males exhibit a marker X chromosome. Such a marker has a secondary constriction or fragile site in band q27 or 28 and is usually seen in 8-50% of the cultured leukocytes from affected males. Data suggest that medium 199 is required to insure the detection of the marker X in leukocyte cultures. The objective of this proposal is to determine the component(s) of medium 199 that results in the appearance of the marker X chromosome and to determine if the medium composition can be manipulated to increase the frequency of the marker X. The application of this data to clinical genetics would allow better diagnosis of affected males, detection of carrier females in such families and, ultimately, the possibility of in utero diagnosis by amniocentesis if these culture conditions can be applied to cultured cells in monolayer.